Effective Ultraslow Low-Dose Thrombolysis for Aortic Bioprosthetic Valve Thrombosis

Abstract

Background

Bioprosthetic valve thrombosis (BPVT) is rare, with an incidence of 0.2% to 6.0%. It often presents as heart failure, thromboembolism, or a new murmur. Diagnosis relies on transthoracic and transesophageal echocardiography, with treatment traditionally being surgical.

Case Summary

We report a 74-year-old patient with valvular and Chagas-related heart disease who developed BPVT of the aortic valve. Owing to high surgical risk and lack of response to heparin, ultraslow low-dose thrombolysis was performed, achieving a successful outcome.

Discussion

The emerging therapies for BPVT have a lower risk of mortality when compared with surgical management. Although to our knowledge there are no studies regarding the use of ultraslow low-dose thrombolysis on patients with aortic BPVT, this case demonstrates the safety and efficacy of this approach.

Visual Summary

Bioprosthetic valve thrombosis (BPVT) is rare, with a prevalence of 0.61% to 0.70% and an incidence of 0.2% to 6.0%,¹ likely underestimated owing to subclinical cases, diagnostic limitations, and lack of a universal definition. Although less thrombogenic than mechanical valves, BPVT mainly affects the mitral and tricuspid valves, then the aortic and transcatheter valves.¹ Risk factors include patient-related conditions, early suboptimal anticoagulation, and valve-related factors^{1 2}. Clinical manifestations range from dyspnea, syncope, and acute heart failure to thromboembolism or subclinical presentations.^1,2

Take-Home Message

• •Further studies are needed to evaluate mortality outcomes and thrombosis resolution after ultraslow, low-dose alteplase in patients with BPVT.

Diagnosis is based on transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE), with predictors such as >50% gradient increase within 5 years (without high output), leaflet thickening >2 mm, and abnormal cusp motion.¹ When echocardiography is inconclusive, cardiac computed tomography can offer detailed assessment.³

Management involves warfarin anticoagulation in stable patients. The 2017 American Heart Association/American Association of Thoracic Surgeons (AHA/ACC) guidelines propose ultraslow low-dose fibrinolysis for patients with mechanical prosthetic valve thrombosis and high surgical or bleeding risk.

Case Summary

We present the case of a 74-year-old man with valvular and Chagas-related heart disease (preserved ejection fraction, apical aneurysm) and congenital bileaflet aortic valve with severe stenosis who underwent biological aortic valve replacement (St. Jude Medical; Epic 23-mm porcine stented bioprosthesis, Abbott) in July 2022. Outpatient medications included aspirin 81 mg, telmisartan/amlodipine 80/5 mg, omeprazole 20 mg, metoprolol succinate 50 mg, and rosuvastatin/ezetimibe 40/10 mg daily.

He was admitted in August 2023 with NYHA functional class II/IV deterioration, dyspnea on exertion, paroxysmal nocturnal dyspnea, and lower limb edema. Vital signs were as follows: blood pressure: 98/70 mm Hg, heart rate: 68 beats/min, respiratory rate: 17 breaths/min, oxygen saturation: 90%, afebrile. Physical examination revealed grade 2 jugular engorgement, crescendo-decrescendo systolic murmur at the aortic area, bibasilar rales, and grade 3 pitting edema. The patient was diagnosed with acute decompensated heart failure.

Electrocardiogram showed sinus rhythm with complete right bundle branch block. Laboratory tests were as follows: N-terminal pro–B-type natriuretic peptide: 4,600 pg/mL, creatinine: 0.95 mg/dL, normal coagulation, hemoglobin: 13.8 g/dL, normal thyroid-stimulating hormone, low-density lipoprotein: 34.8 mg/dL, high-density lipoprotein: 26.7 mg/dL, total cholesterol: 82.7 mg/dL, and glycosylated hemoglobin: 5.7%.

TTE showed preserved ejection fraction (59%), concentric hypertrophy, and dysfunction of the bioprosthesis, with severe stenosis and mild regurgitation. The outflow tract measured 2.0 cm; the maximum velocity was 4.78 m/s, maximum gradient was 91.48 mm Hg, and mean gradient was 65.58 mm Hg. TEE showed increased echogenicity at the noncoronary leaflet arterial portion, suggestive of thrombus (Figures 1A and 2A). Differential diagnoses such as prosthetic valve endocarditis were ruled out (negative blood cultures).

Figure 1.

Evidence of Hyperechogenic Image in the Aortic Valve

(A) Initial transesophageal echocardiography showing hyperechoic image in biological aortic valve. (B) Transesophageal echocardiography after treatment with unfractionated heparin showing significant increase in image size.

Figure 2.

Post-Thrombolysis Echocardiographic Resolution of Aortic BPVT

Post-thrombolysis transthoracic echocardiography with low-dose alteplase in an ultraslow infusion. The aortic valve is observed without biological evidence of thrombi or thickening of the leaflets in the long (A) and short (B) parasternal axis.

Heparin infusion (1,300 IU/h, no bolus) was initiated. After 1 week with therapeutic partial thromboplastin times, follow-up TEE showed persistent severe prosthesis dysfunction. Three-dimensional reconstruction identified leaflet thickening at the base of the noncoronary cusp, with restricted opening. The outflow tract measured 2.1 cm; the maximum velocity was 5.11 m/s and the maximum gradient was 104.46 mm Hg (Figure 1B).

The heart team decided on fibrinolysis with a low-dose protocol of alteplase in an ultraslow infusion (25 mg for 24 hours). The patient did not present any episode of bleeding or complications during or after the infusion. The postinfusion control TTE showed improvement in cusp movement and a notable decrease in peak velocity and mean transprosthetic gradient as well as acceleration time with normal control and a normal Doppler velocity index, which suggested normal function. In addition, there was a decrease in the severity of mitral insufficiency as a possible reflection of improvement in left ventricular systolic pressure (Figures 2B, 3A, and 3B).

Figure 3.

Gradients in Aortic Bioprosthetic Valve Before and After Thrombolysis

(A) Initial transesophageal echocardiography showing markedly elevated gradients and velocities in the aortic valve prosthesis on continuous Doppler. (B) Post-thrombolysis transthoracic echocardiogram with low-dose alteplase in an ultraslow infusion; normalization of velocities and gradients is observed in continuous Doppler.

Case Outcome and Follow-Up

Symptoms resolved post-thrombolysis, and echocardiography showed normalization of prosthetic valve function. No recurrence of thrombosis or heart failure was seen during the 12-month follow-up.

Discussion

BPVT is rare (prevalence: 0.61%-0.70%), with mortality ranging from 4% (NYHA functional class I) to 18% (NYHA functional class III).¹ Though less thrombogenic than mechanical valves, it mostly affects the mitral and tricuspid valves, followed by the aortic and transcatheter valves.¹ Risk factors include patient-related conditions (chronic kidney disease, atrial fibrillation, hypercoagulability, diabetes mellitus, low output, poor anticoagulation) and valve-related factors (porcine stented valves, structural deterioration).^1,2 Clinical presentation ranges from dyspnea to subclinical forms, and the condition is classified as acute (<3 days), subacute (3 days–3 months), late (3-12 months), and very late (>1 year).³ Our patient had very late thrombosis, likely related to endothelial dysfunction, Chagas disease–related hypercoagulability, and a porcine pericardial stented bioprosthesis.⁴

Diagnosis of BPVT can be difficult owing to mimics such as endocarditis or pannus. In bioprostheses, thrombosis typically shows leaflet thickening with raised gradients, as in our patient.³ The 2020 ACC/AHA guidelines (Class 2a) recommend three-dimensional TEE or cardiac computed tomography to assess leaflet motion and thrombus extent.⁵ If echo is inconclusive, cardiac computed tomography is advised.³ Findings on computed tomography include hypoattenuated thickening; attenuation of <90 HU suggests acute thrombus, while attenuation from 90 to 145 HU suggests chronic thrombus.⁶ Pannus shows attenuation similar to septal tissue.⁶ Thrombosis usually occurs in the atrial (mitral) or arterial (aortic) regions, while pannus appears ventricular.⁷ The ACC/AHA guidelines recommend vitamin K agonists for stable BPVT (Class 2a, Level of Evidence: B), whereas obstructive or symptomatic cases may need thrombolysis or surgery.⁵ Initially, the European Society of Cardiology/European Association for Cardiothoracic Surgery guidelines favored surgery, but since 2022, slow-infusion low-dose thrombolysis has also been endorsed.⁸

The PROMETEE (PROsthetic MEchanical valve Thrombosis and the prEdictors of outcomE) study showed greater success with ultraslow tissue-type plasminogen activator (alteplase 25 mg/24 h) in patients assessed as NYHA functional class I to III.⁹ The HATTUSHA (Hatay Study of Ultraslow Thrombolytic Therapy in Prosthetic Heart Valve Thrombosis) study found this approach safe and effective for obstructive mechanical valve thrombosis.¹⁰ Both studies were conducted among patients with mechanical prosthetic valve thrombosis.

Although ultraslow low-dose thrombolysis is currently supported and studied primarily in patients with mechanical prosthetic valve thrombosis, there is no established clinical guideline or robust evidence supporting its use in BPVT. In this case, we successfully implemented ultraslow low-dose thrombolysis in a patient with confirmed BPVT and high surgical risk, resulting in complete clinical and echocardiographic resolution without complications. This represents a unique and clinically relevant scenario that may support the rationale for future prospective studies or clinical trials evaluating the safety and efficacy of this therapeutic strategy in patients with bioprosthetic valves.

Visual Summary.

Ultraslow Thrombolysis in Aortic BPVT: A Case Overview

BPVT = bioprosthetic valve thrombosis; IgG = immunoglobulin G; MRI = magnetic resonance imaging; TEE = transesophageal echocardiography; TTE = transthoracic echocardiography.

Conclusions

This case illustrates the potential role of ultraslow low-dose alteplase thrombolysis (25 mg/24 h) in managing BPVT of the aortic valve, especially when surgery is high risk and anticoagulation alone is insufficient. Further studies are needed to clarify the efficacy and safety of this approach in patients with BPVT.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Video 1

TEE After Heparin Infusion: First Part, 3D Reconstruction

Video 2

TEE After Heparin Infusion: Second Part, 3D Reconstruction

Video 3

TEE After Heparin Infusion: Third Part, 3D Reconstruction

Video 4

Initial TEE: First Part

Video 5

Initial TEE: Second Part

Video 6

TTE After Ultraslow Thrombolysis: First Part

Video 7

TTE After Ultraslow Thrombolysis: Second Part